<p>Conventional methods for measuring antibacterial activity, such as disk-diffusion assays, have limitations in quantitative reliability and require long incubation times making them unsuitable for high-throughput applications. To address these limitations, we automated a turbidity-based assay using readily available equipment and Bayesian data analysis, enabling accurate and precise antibacterial quantification from high-throughput experiments. In this study, we demonstrate the method applied to lysostaphin, a potent anti-staphylococcal agent and promising candidate for therapeutic applications. The turbidity assay monitors optical density changes upon lysostaphin-induced lysis of a susceptible <i>Staphylococcus</i> strain. We validated the use of autoclaved <i>Staphylococcus&#xa0;carnosus</i>&#xa0;TM300 as suitable indicator strain and optimized assay conditions for dynamic range of 0.63–10&#xa0;mg&#xa0;L<sup>−1</sup> lysostaphin. Our integrated approach provides a robust, scalable, and reproducible platform for quantifying active lysostaphin, paving the way for its application in high-throughput screening and process development. We believe that the approach is adaptable to other turbidity-based assays, such as those assessing endolysin activity.</p>

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Turbid but accurate: automating lysostaphin quantification including uncertainty quantification

  • Lisa Prigolovkin,
  • Michael Osthege,
  • Maximilian Siska,
  • Josefin Sander,
  • Anja Hoffzimmer,
  • Wolfgang Wiechert,
  • Christian K. Desiderato,
  • Christian U. Riedel,
  • Marco Oldiges

摘要

Conventional methods for measuring antibacterial activity, such as disk-diffusion assays, have limitations in quantitative reliability and require long incubation times making them unsuitable for high-throughput applications. To address these limitations, we automated a turbidity-based assay using readily available equipment and Bayesian data analysis, enabling accurate and precise antibacterial quantification from high-throughput experiments. In this study, we demonstrate the method applied to lysostaphin, a potent anti-staphylococcal agent and promising candidate for therapeutic applications. The turbidity assay monitors optical density changes upon lysostaphin-induced lysis of a susceptible Staphylococcus strain. We validated the use of autoclaved Staphylococcus carnosus TM300 as suitable indicator strain and optimized assay conditions for dynamic range of 0.63–10 mg L−1 lysostaphin. Our integrated approach provides a robust, scalable, and reproducible platform for quantifying active lysostaphin, paving the way for its application in high-throughput screening and process development. We believe that the approach is adaptable to other turbidity-based assays, such as those assessing endolysin activity.